Tan, June et al. (2013) International Worm Meeting "Combining genomic approaches to characterize alternative splicing events in C. elegans."

Na, Hong, Fraser, Andrew, Ray, Debashish, Hughes, Timothy, Ramani, Arun, Tan, June

[International Worm Meeting, 2013]

Alternative splicing (AS) is a highly regulated process that contributes to proteome complexity. With recent advances in sequencing and other high-throughput technologies, our knowledge of the many AS events in C. elegans has rapidly increased. However, for many of these events, it is still not known which splicing factors are involved, and how they function to regulate each splicing decision. We have generated RNA-Seq, RNA binding, and genetic interaction data for several splicing factors to model how these factors regulate different AS events- whether individually, or combinatorially with other splicing factors. We have identified AS events that are perturbed in several splicing factor-defective backgrounds- including loss-of-function of asd-1, fox-1, mec-8, sym-2 and exc-7. Combining this data with RNA-binding specificities for these splicing factors, we have identified genes that are likely direct targets of these splicing factors, and are in the process of validating these splicing targets in vivo. In addition, we systematically probed for other factors that genetically interact with these splicing factors by screening an RNAi library targeting ~400 genes containing known or predicted RNA-binding domains. Scoring for enhanced population fitness defects, we have identified interactions with components of the spliceosome, regulatory splicing factors, as well as other factors involved in mRNA-processing. We are using this data as an added resource to predict factors that may function in the same splicing regulatory pathways, to identify instances of combinatorial splicing regulation.

Tan, June et al. (2015) International Worm Meeting "Genomic approaches to study the roles of various splicing factors in regulating alternative splicing events in C. elegans."

Tan, June, Na, Hong, Fraser, Andrew G., Ramani, Arun K., Morris, Quaid, Hughes, Timothy R., Ray, Debashish

[International Worm Meeting, 2015]

Alternative splicing (AS) is a highly regulated process. Mutations in trans-acting splicing factors that disrupt AS have been implicated in human diseases, such as muscular dystrophy and autoimmune diseases. Our goal is to combine several genome-scale approaches to examine how multiple splicing factors can work in concert to regulate AS events in C. elegans. In particular, we focused on 5 splicing factors that are expressed in the neuromuscular system, and that have functional interactions with one another. We have generated RNA-Seq data to identify AS events that are differentially regulated in mutants of asd-1, fox-1, mec-8, sym-2 and exc-7. We have also obtained in vitro RNA-binding specificity data- derived using the RNAcompete method- that allows us to then predict direct targets for each splicing factor. In addition, we have screened for genetic interactions between these splicing factors and several other RNA-binding proteins that may function in the same splicing pathways. Here, we will present a summary of these individual datasets and focus specifically on the intriguing finding that these splicing factors seem to regulate splicing of many of the same targets. We will also highlight other findings, including how requirement for a splicing factor can change across development, and how AS can differ between natural isolates. Together, our data provide insight into how AS of specific sets of genes are regulated in C. elegans, and how defects in splicing of these genes could lead to neuromuscular defects.

Ji K et al. (2015) Food Funct "Inhibition effects of tanshinone on the aggregation of -synuclein."

Liu Y, Ji K, Zhao Y, Yang X, Gong H, Huang K, Wang Z, Yu T

[Food Funct, 2015]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Lewy bodies that are formed by the aggregated -synuclein are a major pathological feature of PD. Salvia miltiorrhiza has been used as food and as a traditional medicine for centuries in China, with tanshinone I (TAN I) and tanshinone IIA (TAN IIA) as its major bioactive ingredients. Here, we investigated the effects of TAN I and TAN IIA on -synuclein aggregation both in vitro and in a transgenic Caenorhabditis elegans PD model (NL5901). We demonstrated that TAN I and TAN IIA inhibited the aggregation of -synuclein as demonstrated by the prolonged lag time and the reduced thioflavin-T fluorescence intensity; TAN I and TAN IIA also disaggregated preformed mature fibrils in vitro. Moreover, the presence of TAN I or TAN IIA affected the secondary structural transformation of -synuclein from unstructured coils to -sheets, and alleviated the membrane disruption caused by aggregated -synuclein in vitro. Besides, the immuno-dot-blot assay indicated that TAN I and TAN IIA reduce the formation of oligomers and fibrils. We further found that TAN I and TAN IIA extended the life span of NL5901, a strain of transgenic C. elegans that expresses human -synuclein, possibly by attenuating the aggregation of -synuclein. Taken together, our results suggested that TAN I and TAN IIA may be explored further as potential candidates for the prevention and treatment of PD.

Chalasani SH et al. (2007) Genome Biol "Global 'worming'."

Feinberg EH, Hilliard MA, Chalasani SH

[Genome Biol, 2007]

: A report on the 16th International Caenorhabditis elegans Meeting, Los Angeles, USA, 27 June-1 July 2007.

Zhang X et al. (2022) Free Radic Biol Med "Tanshinone IIA loaded chitosan nanoparticles decrease toxicity of β-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease"

Zhang X, Chang Y, Du L, Wang J, Zhang L, Wang S, Kang X, Liu Y, Zhao Y, Huang Y

[Free Radic Biol Med, 2022]

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases that characterized by the accumulation of β-amyloid peptide (Aβ). Overexpressions of Aβ could induce oxidative stress that might be a key insult to initiate the cascades of Aβ accumulation. As a result, anti-oxidative stress and attenuating Aβ accumulation might be one promising intervention for AD treatment. Tanshinone IIA (Tan IIA), a major component of lipophilic tanshinones in Danshen, is proven to be effective in several diseases, including AD. Due to the poor solubility in water, the clinical application of Tan IIA was limited. Therefore, a great number of nanoparticles were designed to overcome this issue. In the current study, we choose chitson as delivery carrier to load Tanshinone IIA (CS@Tan IIA) and explore the protective effects of CS@Tan IIA on the CL2006 strain, a transgenic C. elegans of AD model organism. Compared with Tan IIA monomer, CS@Tan IIA could significantly prolong the lifespan and attenuate the AD-like symptoms, including reducing paralysis and the Aβ deposition by inhibiting the oxidative stress. The mechanism study showed that the protection of CS@Tan IIA was attenuated by knockdown of daf-16 gene, but not skn-1. The results indicated that DAF-16/SOD-3 pathway was required in the protective effects of CS@Tan IIA. Besides DAF-16/SOD-3 pathway, the Tan IIA-loaded CS nanoparticles might protect the C. elegans against the AD insults via promoting autophagy. All the results consistently suggested that coating by chitosan could improve the solubility of Tan IIA and effectively enhance the protective effects of Tan IIA on AD, which might provide a potential drug loading approach for the hydrophobic drugs as Tan IIA.

Dahl JL et al. (2011) J Bacteriol "Role of phase variation in the resistance of Myxococcus xanthus fruiting bodies to Caenorhabditis elegans predation."

Ulrich CH, Kroft TL, Dahl JL

[J Bacteriol, 2011]

The phenomenon of phase variation between yellow and tan forms of Myxococcus xanthus has been recognized for several decades, but it is not known what role this variation may play in the ecology of myxobacteria. We confirm an earlier report that tan variants are disproportionately more numerous in the resulting spore population of a M. xanthus fruiting body than the tan vegetative cells that contributed to fruiting body formation. However, we found that tan cells may not require yellow cells for fruiting body formation or starvation-induced sporulation of tan cells. Here we report three differences between the yellow and tan variants that may play important roles in the soil ecology of M. xanthus. Specifically, the yellow variant is more capable of forming biofilms, is more sensitive to lysozyme, and is more resistant to ingestion by bacteriophagous nematodes. We also show that the myxobacterial fruiting body is more resistant to predation by worms than are dispersed M. xanthus cells.

Muir RE et al. (2008) Appl Environ Microbiol "Virulence of Leucobacter chromiireducens subsp. solipictus to Caenorhabditis elegans: characterization of a novel host-pathogen interaction."

Tan MW, Muir RE

[Appl Environ Microbiol, 2008]

We describe the pathogenic interaction between a newly described Gram-positive bacterium Leucobacter chromiireducens subsp. solipictus strain TAN 31504 and the nematode Caenorhabditis elegans. TAN 31504 pathogenesis on C. elegans is exerted primarily through infection of the adult nematode uterus. TAN 31504 enters the uterus through the external vulval opening and the ensuing uterine infection is strongly correlated with a significant reduction in host life span. Young worms can fed and develop on TAN 31504, but not preferably over the standard food source. C. elegans reared on TAN 31504 as the sole food source develop into thin adults with little intestinal fat stores, produce few progeny, and subsequently can not persist on the pathogenic food source. Within 12 h of exposure, adult worms challenged with TAN 31504 alter the expression of a number of C. elegans innate immunity-related genes, including nlp-29, which encodes a neuropeptide-like protein. C. elegans exposed briefly to TAN 31504 develop lethal uterine infections analogous to worms exposed continuously to pathogen, suggesting that mere contact with the pathogen is sufficient for the host to become infected. TAN 31504 produces a robust biofilm and this behavior is speculated to play a role in the virulence exerted on the nematode host. The interaction between TAN 31504 and C. elegans provides a convenient opportunity to study bacterial virulence on nematode tissues other than the intestine and may allow for the discovery of host innate immunity elicited specifically in response to vulval-uterine infection.

Cordero F et al. (2019) BMC Bioinformatics "BITS2018: the fifteenth annual meeting of the Italian Society of Bioinformatics."

Cordero F, Calogero RA, Caselle M

[BMC Bioinformatics, 2019]

This preface introduces the content of the BioMed Central Bioinformatics journal Supplement related to the 15th annual meeting of the Bioinformatics Italian Society, BITS2018. The Conference was held in Torino, Italy, from June 27th to 29th, 2018.

Muir RE et al. (2007) Int J Syst Evol Microbiol "Leucobacter chromiireducens subsp. solipictus subsp. nov., a pigmented bacterium isolated from the nematode Caenorhabditis elegans, and emended description of L. chromiireducens."

Muir RE, Tan MW

[Int J Syst Evol Microbiol, 2007]

A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming, irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell-wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number of shared biochemical characteristics, strain TAN 31504(T) was placed in the genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG 22506(T) indicating that these two strains belong to the same species, when the recommended threshold value of 70 % DNA-DNA relatedness for the definition of a bacterial species by the ad hoc committee on reconciliation of approaches to bacterial systematics is considered. Based on distinct differences in morphology, physiology, chemotaxonomic markers and various biochemical characteristics, it is proposed to split the species L. chromiireducens into two novel subspecies, Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L-1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp. solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).

Mlot C (1991) Science "A well-rounded worm."

Mlot C

[Science, 1991]

The millimeter-long roundworm Caenorhabditis elegans is amassing a sizable research following. As more and more people have joined teh confederation of research efforts loosely called the worm project (see Science, 15 June 1990, p. 1310), the community's biennial meeting has outgrown the traditional watering hole at Cold Spring Harbor. This year, the researchers moved inland for the Eighth International C. elegans Meeting, held June 1-5 on Lake Mendota at the University of Wisconsin, Madison. More than 500 "worm people" turned out to absorb progress reports on the sequencing of the C. elegans genome, the study of its developmental pathways-and some newer topics as well.